Concomitant necrotizing encephalitis and granulomatous meningoencephalitis in four toy breed dogs

Abstract

The term "meningoencephalitis of unknown origin" (MUO) describes a group of different encephalitides in dogs in which no infectious agent can be identified and a multifactorial etiology is suspected. Among others, genetic factors and unknown triggers seem to be involved. Included are necrotizing leukoencephalitis (NLE), necrotizing meningoencephalitis (NME), and granulomatous meningoencephalitis (GME). In this case series, we describe the histopathological findings of four toy breed dogs with focal or multifocal necrotizing encephalitis and mainly lymphocytic perivascular infiltrates on histopathological examination. At the same time, however, in all dogs, focal or multifocal high-grade angiocentric granulomatous inflammatory lesions were evident with focal histiocytic perivascular infiltrates in the brain. The former changes are typical for NLE and NME. In contrast, the latter changes are indicative of GME. This case series shows that the boundaries between the necrotizing and granulomatous variants of MUO might be smooth and suggests that NLE, NME, and GME are not as distinct as previously described. This finding could be a crucial piece of the puzzle in the study of the pathogenesis of MUO as individual susceptibility and specific triggers could be responsible for the manifestation of the different MUO subtypes.

Keywords: canine (dog); granulomatous meningoencephalitis (GME); histopathology (HPE); inflammatory brain disease; meningoencephalitis of unknown origin (MUO); necrotizing leukoencephalitis; necrotizing meningoencephalitis.

Figure 1

Magnetic resonance imaging (MRI) of a Yorkshire Terrier with meningoencephalitis of unknown origin (case 1). Transverse plane at the level of the mesencephalon (A,B) and interthalamic adhesion (C) (see blue lines in the schematic overview upper right), A: T2 weighted (w), B, C: T1w post contrast injection. Intraaxial lesion of the subcortical white matter of the cerebral hemisphere, identified on histopathology as predominantly necrotic (A,B: white arrow). Intraaxial lesion of the striated body identified as granulomatous lesion (C: blue arrow).

Figure 2

Combined necrotizing leukoencephalitis and granulomatous meningoencephalitis in the brain of a Yorkshire Terrier (case 1). (A) right striatal body; marked granulomatous inflammation with severe lymphocytic perivascular cuffing. (B) cerebrum, left parietal lobe; marked necrotizing leukoencephalitis in subcortical white matter with gitter cells (malacia) and severe lymphohistiocytic perivascular cuffing; bars = 500 μm.

Figure 3

Combined necrotizing and granulomatous meningoencephalitis in the brain of a Maltese (case 2). (A) Focal-extensive malacia in the midbrain (arrows). (B) Subgross picture of a H&E stained section of the midbrain shown in A. Focal-extensive pallor indicates necrosis and edema, which is associated with a prominent inflammatory process (dark blue color due to nuclei of infiltrating inflammatory cells). (C) Area of granulomatous inflammation with lymphocytes (arrows) and activated macrophages (arrowheads) around a vessel. The activated macrophages markedly extend into the neuroparenchyma (asterisk).

Figure 4

Combined necrotizing and granulomatous meningoencephalitis in the brain of a Yorkshire Terrier (case 3). (A) Severe, focal-extensive and delineated malacia in the right rhinal cortex and extending to the surface. This lesion mimicks NME. Additionally, there are multifocal areas of beige discoloration in the corona radiata (arrows). (B) Severe and multifocal-coalescing perivascular cuffs with lymphocytes and large activated macrophages. Macrophages tend to compartmentalize within these cuffs. (C) The same dog is affected by a marked cerebellar meningitis that extends into the molecular layer.